Brain-derived neurotrophic factor signaling and Acetylcholinesterase (BDNF/AChE)

The term BDNF-related neurotrophic signaling and acetylcholinesterase refers to a dual-target therapeutic framework primarily relevant to neurodegenerative disorders like Alzheimer's disease. Brain-Derived Neurotrophic Factor (BDNF) is a critical growth factor that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses through its primary receptor, Tropomyosin receptor kinase B (TrkB) [1, 3]. Acetylcholinesterase (AChE) is an enzyme that terminates signal transmission at cholinergic synapses by rapidly hydrolyzing the neurotransmitter acetylcholine [2]. In Alzheimer's disease, a significant loss of cholinergic neurons and a decrease in BDNF levels contribute to cognitive decline and neuronal death [5]. Drugs targeting this dual system, such as acetylcholinesterase inhibitors (AChEIs), aim to increase acetylcholine levels to improve symptoms, while experimental therapies seek to simultaneously enhance BDNF signaling to provide disease-modifying neuroprotection [4, 5]. This integrated approach is a major focus of multi-target directed ligand (MTDL) development designed to address the complex pathology of dementia [5]. Citations: [1] UniProt P23560; [2] UniProt P22303; [3] UniProt P15260; [4] StatPearls, Cholinesterase Inhibitors; [5] PMID: 24991016.

Other names

BDNF-TrkB pathway and AChENeurotrophic-cholinergic axisBDNF-AChE signaling complex

Inhibition of acetylcholinesterase to increase synaptic acetylcholine levels combined with the modulation of BDNF/TrkB signaling to enhance neuronal survival and plasticity.